The Role of Lactobacillus Reuteri in Children and Adolescents With Anorexia Nervosa

The Role of Lactobacillus Reuteri in Nutritional Recovery and Treatment of Constipation in Children and Adolescents With Anorexia Nervosa - Randomised, Double Blind, Placebo Controlled Study

The aim of this study is to investigate whether Lactobacillus reuteri could have a beneficial role in treatment of children and adolescents with Anorexia nervosa who develop motility disorder due to the malnutrition regarding the normalization of the motility, as well as the possible role of probiotics on nutritional recovery, especially on bone health.

Study Overview

• Status: Completed
• Conditions: Anorexia Nervosa; Constipation
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri Protectis DSM17938

Detailed Description

Pediatric patients with AN and constipation referred to gastroenterologist for nutritional rehabilitation at the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Clinical Hospital Center Sestre Milosrdnice, Zagreb, approximately 30 children, will be asked to participate.

The evaluation of patients will be conducted through APA DSM-V diagnostic criteria for anorexia nervosa and Rome III criteria for constipation.

During the hospitalization all of the patients will receive conventional nutritional rehabilitation that is composed of serving normal food under supervision of nurses that calculate daily caloric intake through 5-6 meals and according to that additional enteral nutrition that consist of polymeric enteral formula. Daily caloric intake is calculated as kcal/kg/day and is slowly rising through 2 weeks starting from 80% to the goal of 130% of daily energy requirements according to FAO 2004 recommendation.

Anthropometry measures will be taken at the time of hospitalization and at every visit.

Normalization of weight is when the Z-score for BMI is less than -1.5 according to CDC BMI-growth charts, or normalisation of menstrual cycle is achieved.

In order to achieve adherence to therapeutic protocol parents will be contacted by phone at least once in 7-10 days. Participants will be instructed to keep diary on a daily basis (adherence to therapy, stool diary). All patients will return packages with all used, and unused product.

BASELINE -VISIT 1 Randomization at first day of hospitalization. In all patients anthropometry will be performed at the time of hospitalization, as well as dual-energy X-ray absorptiometry (DEXA) and serum D3 levels at first 2 days of hospitalization as a part of routine diagnostic protocol in heavily underweight patients with AN.

VISIT 2 4 weeks after randomization, at discharge from hospital Anthropometry

VISIT 3 8 weeks after randomization, 4 weeks after discharge from hospital Anthropometry

END OF STUDY -VISIT 4 3 months after baseline Anthropometry

VISIT 5 3 months after the end of study (6 months after baseline) At this point control serum D3 levels and DEXA will be performed at all patients Anthropometry

All the symptoms and daily caloric intake will be monitored using diaries attached to protocol.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Croatia
  • Zagreb, Croatia
    • Pediatric Department Clinical Hospital Centre Sestre milosrdnice Gastroenterology, Hepatology and Nutrition Ward

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric patients with Anorexia nervosa and constipation, aged 8-18 years

Exclusion Criteria:

• AN and constipation present for less than 3 month prior to hospitalization
• any disease that affects GI or other systems other than AN or functional constipation
• chronic disorder other than AN
• receiving probiotic and/or prebiotic products 14 days prior to enrolment
• receiving antibiotics 14 days prior to enrolment
• constipation prior AN
• receiving laxative as a therapy for constipation or abuse of laxative to lose weight prior to enrolment
• extraintestinal symptoms: fever, rash
• abnormalities in laboratory findings
• abnormalities in clinical findings: organomegaly, perianal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactobacillus reuteri Protectis DSM17938; One chewable tablet twice per day with L reuteri Protectis DSM 17938, 1x108 CFU/tablet (colony forming unit)	Dietary supplement: Lactobacillus reuteri Protectis DSM17938; One chewable tablet with L. reuteri or placebo taken twice a day for 3 months. After the 3 month therapy both groups will be monitored for the next 3 months.
Placebo Comparator: Placebo; One chewable tablet twice per day with placebo per day	Dietary supplement: Lactobacillus reuteri Protectis DSM17938; One chewable tablet with L. reuteri or placebo taken twice a day for 3 months. After the 3 month therapy both groups will be monitored for the next 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Drop Out From Rome III Criteria for Constipation	Drop out from Rome III criteria for constipation: Yes / No. According to Rome III, a diagnosis of functional constipation is made when at least two of the following criteria are met for the last 3 months with symptom onset at least 6 months prior to diagnosis: a) straining on >25% of defecations; b) lumpy or hard stools on >25% of defecations; c) sensation of incomplete evacuation on >25% of defecations; d) sensation of anorectal obstruction/blockage on >25% of defecations; e) manual maneuvers on >25% of defecations; and f) less than 3 defecations per week.	3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalization of Body Weight	normalization of body weight- 90% of premorbid weight, or ≥10. centile for BMI (according to the WHO growth charts)	6 month

Collaborators and Investigators

• Sponsor: BioGaia AB
• Investigators: Principal Investigator: Orjena Zaja Franulovic, MD, PhD, Center for Eating disorders Sestre milosrdnice University hospital Zagreb, Croatia

Publications and helpful links

General Publications

• Žaja O, Fiolić M, Ćuk MC, Tiljak MK. "The role of L. reuteri DSM17938 in nutritional recovery and treatment of constipation in children and adolescents with anorexia nervosa - a randomized, double blind, placebo controlled study". Clin Nutr ESPEN. 2021 Dec;46:47-53. doi: 10.1016/j.clnesp.2021.08.016. Epub 2021 Sep 8.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 6, 2013
• First Posted (Estimate): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Constipation; Probiotics; Body weight; Anorexia nervosa
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Feeding and Eating Disorders; Anorexia; Anorexia Nervosa; Constipation
• Other Study ID Numbers: CSUB0083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No